We are proposing to improve the existing ISFETs by changing the structure of these devices. A conducting layer will be incorporated into the gate insulator. It will be electrically shorted to the substrate all the time except during the measurement when it will be floated. In the shorted state, the device is electrostatically protected, it can be "burned-in," calibrated and tested. This improvement should eliminate the major outstanding problem which is restricting the use of these devices - their vulnerability to electrostatic damage. It will also greatly improve the calibration and testing procedure. Our preliminary results indicate enzymatically active transistors are possible. We are proposing to develop FETs sensitive to urea, creatinine, lactate and other substrates. The lactate FET which is based on the measurement of the ratio of NAD/NADH will serve as a model for other redox enzyme systems. A submicron tip ISFET is already in an advanced stage of development. We shall complete the development of Ca ions, Na ion, H ion, and Cl ions micron ISFETs and make them available oxygen binding organometallic compounds. It is hoped that this sensor will be more stable and reproducible then Clark oxygen electrode. Excellent preliminary results were obtained with combined flow injection analysis and ISFETs. A portable multi-ion analyzer for biological fluids can be constructed. We will design a simple multiple gate chip which will serve as an ISFET detector for this system. We shall provide existing ISFETs as well as newly developed and improved ones to the ongiong medical research at the University of Utah, Departments of Surgery, Anesthesiology, and Physiology.